Nitric Oxide Reduces Vagal Baroreflex Sensitivity in the Late Gestation Fetus

Abstract

Goals to understand the etiology of essential hypertension have proposed that this problem arises, in part, because of changes within brainstem circuits involved in arterial blood pressure (ABP) control. It has been suggested that nitric oxide (NO) exerts inhibitory influences on the integration of afferent discharge from the arterial baroreceptors. This study tested the hypothesis that the inhibitory influence of NO on the arterial baroreflex is present in fetal life. Fetal baroreflex sensitivity was calculated in fetal sheep, before and during the NO-clamp; a technique that permits NO synthase (NOS) blockade with L-NAME while maintaining basal cardiovascular function with sodium nitroprusside. Under halothane anesthesia, five fetal sheep at 0.8 gestation were instrumented with vascular catheters. Five days later, fetuses received a range of bolus doses of phenylephrine (5-75 g I.A.) in randomized order either during saline or treatment with the NO clamp. Basal fetal ABP and heart rate before (50 Ϯ 4 mm Hg, 170 Ϯ 3 bpm) or during (51 Ϯ 4 mm Hg, 173 Ϯ 3 bpm) the NO-clamp were similar. The gradient of the pulse interval-ABP relationship was nearly doubled during NOS blockade (14.2 Ϯ 2.5 versus 7.8 Ϯ 1.6 ms/mm Hg). The data provide in vivo evidence that NO attenuates the sensitivity of the cardiac baroreflex during fetal life. (Pediatr Res 65: 269-273, 2009) T he arterial baroreflex plays an important role in maintaining cardiovascular homeostasis by continuously eliciting autonomic adjustments to maintain arterial blood pressure (ABP) within a narrow physiologic range. Baroreceptors are located in the carotid sinus and aortic arch, where they sense beat-by-beat changes in ABP. This information is relayed via primary afferent neurons to the brainstem, where the signal is processed and integrated. Compensatory adjustments in heart rate (HR) and vascular resistance, for any perturbations in ABP, are subsequently mediated via changes in efferent vagal and sympathetic outflow (1,2).Studies in both the adult and fetus have shown that there is an age-dependent fall in arterial baroreflex sensitivity (3,4). Accumulating evidence implicates nitric oxide (NO) in baroreflex pathways and its involvement in altering baroreflex sensitivity with ageing. For instance, NO synthase (NOS) immunoreactivity has been demonstrated in several locations of the baroreflex pathway, including the carotid sinus (5), the nucleus tractus solitarius (6), and the cardiac vagal and preganglionic sympathetic neurons (7,8). Further, the fall in baroreflex sensitivity with advancing age in conscious lambs is dependent on NO (9). However, it remains completely unknown whether the inhibitory influence on baroreflex sensitivity by NO is already present in fetal life. The present study tested the hypothesis that endogenous NO depresses baroreflex sensitivity during fetal life. Our own pilot studies and investigations by Schroder et al. (10) have shown that in fetal life, unloading of the arterial baroreceptors, for instance using bolus doses ...

Vitamin C Prevents Intrauterine Programming of in vivo Cardiovascular Dysfunction in the Rat

“…For instance, it is known that baroreception can be depressed by oxidative stress 48 and by NO. 49, 50 Similarly, oxidant tone and NO within the medulla can alter sympathetic and vagal outflow. 51,52 Whilst systemic administration of vitamin C increases baroreflex sensitivity in the adult, 53 probably via actions on carotid baroreceptors, 48 acute intraventricular administration of vitamin C has been shown to depress baroreflex gain through enhancements of parasympathetic outflow at the level of the NTS and/or nucleus ambiguous.…”

Statin treatment depresses the fetal defence to acute hypoxia via increasing nitric oxide bioavailability

“…More recently, the contribution to these responses of local agents, in particular NO, independent of neuroendocrine control has gathered increasing attention (Morrison et al 2003; Thakor & Giussani, 2009; Thakor et al 2010 b ). Studies have shown that fetal NO bioavailability can increase during acute hypoxia, altering neuroendocrine constrictor influences and metabolic responses (Morrison et al 2003).…”

Ambulatory Cardiovascular Activities in L-NAME-Treated Mice

“…The inhibitory influence of NO on the arterial baroreflex is present in fetal life. The gradient of the pulse interval-arterial BP relationship was nearly doubled during the NOS blockade in fetal sheep, demonstrating that NO attenuates the sensitivity of the cardiac baroreflex during fetal life and that NO exerts inhibitory influences on the integration of afferent discharge from the arterial baroreceptors [37]. Hypertension and bradycardia could either derive from the independent effects of LNAME on vascular tone and HR, from baroreflex interaction, or from a combination thereof.…”